AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2766-2314/019
University Clinic for Rheumatology, faculty of medicine, University Clinical Center “Mother Therese”, Skopje, Republic of North Macedonia.
*Corresponding Author: Dejan Spasovski, University Clinic for Rheumatology, faculty of medicine, University Clinical Center “Mother Therese”, Skopje, Republic of North Macedonia.
Citation: Spasovski D., (2020) Lysosomal or brush border enzymuria in kidney enzyme activities in seronegative rheumatoid arthritis. J, Biotechnology and Bioprocessing 1(3); DOI: 10.31579/2766-2314/019
Copyright: © 2020, Dejan Spasovski, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 04 December 2020 | Accepted: 19 December 2020 | Published: 28 December 2020
Keywords: alanine aminopeptidase; (AAP); gama-glutamyl transferase (gama--GT); β2 microglobulin (β2M); rheumatoid arthritis (RA); rheumatoid factor (RF)
Introduction: To determine the effects of non-treated seronegative rheumatoid arthritis (RA) on proximal renal tubule, sensitivity of Alanine aminopeptidase (AAP), g-glutamyltransferase (g--GT), β2 microglobulin in urine β2M), as well as relation with rheumatoid factor (RF) and C-Reactive protein (CRP), DAS 28 disease activity index.
Methods: RF was determined by agglutination test (Latex RF test, while kinetic methods were used for determination of Alanine aminopeptidase (AAP) and g-glutamyltransferase (g-GT), as well as MEIA (Micro particle Enzyme Immunoassay) to determine β2 microglobulin in urine. Samples (serum and urine) of 70 participants were examined (35 RA not treated, 35 health control group).
Results: In 35 RF negative RA, AAP enzymuria was present in 12 (34.28%) patients, g-GT was present in 7 patients (20%), while β2 microglobulin was present in 3 patients (8.57%). In the healthy control group, 4 patients showed AAP positivity (11.42%), 2 patients g-GT positivity (5.71%) and 1 patient showed presence of β2 microglobulin in urine (2.85). RF was not present in any patient (0%).
Conclusion: AAP has a higher sensitivity of g-GT and b2 microglobulin in the detection of asymptomatic renal lesions in non treated seronegative RA.
Enzymes in urine can derive from plasma, glands of the urogenital tract, epithelial cells of the urinary tract, leukocytes, and erythrocytes [1] and kidneys. There are about 40 different enzymes [2-6] in the urine that belong to different groups: oxidoreductase, transferase, hydrolase, lyase, while isomerases and ligases are not found in the urine. The occurrence of such large number of enzymes in the urine indicates the dominant role of kidneys in their excretion.
Examination of the cell membranes of the brush epithelium of the proximal tubules confirms the localization of alanine aminopeptidase (AAP) in 90%, alaline phosphatase (AF) in 70% and g-glutamyl transpeptidase (g-GT) in 50% of the total activity of these enzymes in the kidney [7-9].
The aim of this study is to determine the effects of non-treated Rheumatoid arthritis on the tubular function AAP, g-GT and β2M being used as indicators for proximal tubular damage.
In patients included in the study, disease diagnose is based on the revised diagnostic criteria for classification of Rheumatoid arthritis proposed in 1987 by the American Rheumatism Association (ARA) [10-13]. For the classification, i.e. the patients to be included in the RA group it is necessary to satisfy at least 4 of the predicted 7 criteria.
Criteria from 1 to 4 were present at least 6 weeks. The study included 35 patients (age 28, age 7) who were diagnosed with seronegative RA, as well as 35 patients (age 18, age 17) as a healthy control group. The average mean age was 48.5 years (± 4.13) (37-65 years) for the RA group, 36.2 years (±10.78) (29-65) for the healthy group. The average time of onset of disease in months from the beginning was 14.97 (± 15.23), in the interval of (1-14) months. None of the patients in the study had a history of previous or current renal impairment. The others negate use of other drugs before sample were taken. The samples were collected in a period of 1 year.
Including criteria
In the study were included patients with RA at the age of 18-65 years, who were not previously treated with NSAIDs or DMARDs.
Excluding criteria
In the study were excluded patients with symptoms or conditions that can directly or indirectly affect the results, such as:
All participants voluntarily took part in this study, so that the criteria to do it are met.
Clinical assessment of disease activity
Clinical assessment and interpretation was made from the subspecialist in the given area. The disease activity was assessed using DAS 28 index. (Disease Activity Score (DAS 28)) [14]. Indexes use mathematical formula to use the unique composite quantitative score consisting of palatable painfully sensitive joints (maximum number 28) and swollen joints (maximum number 28), global assessment for disease activity (0 – 100 mm Visual Analog Scale VAS), as well as morning stiffness (minutes). DAS 28 index ranges from 0 to 10 and score below 3.2 qualifies the disease as low active.
Laboratory assessment
For clinical assessment of disease, it is necessary to consider the following laboratory variables: Complete blood count (CBC) and differential, acute phase reactants, such as C-reactive protein (CRP), Rheumatoid factor (RF), Erythrocyte sedimentation rate (ESR), alkaline phosphatase (AF), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), lactate dehydrogenase (LDH), urea / serum, creatinine / serum.
Urine samples were taken not only for rutine urinary examination, but also for determination of AAP, g-GT, β2M.
Serum urea is determined by the method of "Kassirer"
Reference values: Serum urea (3-7.8 mmol / L).
Creatine in serum and urine and determined by the method of: "Jaffe"
Reference values: Serum creatine 45 - 109 µmol / L; Creatine in urine 7 - 17 mol / dU.
C-reactive protein (CRP) determined by agglutination test (Latex CRP test)
Reference values: < 6>
Rheumatoid factor (RF) determined by agglutination test (Latex RF test)
Reference values: < 8>
Determination of Alanine Aminopeptidase Activity (AAP): Kinetic Method
Reference values: AAP in urine 0.25-0.75 U / mmol creatinine
Determination of g-glutamyltranspeptidase (g-GT) activity: Ifcc method
Valuable referents
g-GT (urine) 0.84-1.80 u / mmol creatinine
Determination of β2 microglobulin (β2M) concentration in urine by the method “meia” ("micro particle enzyme immunoassay")
Reference values:
β2 microglobulin (urine) = 0.02-0.19 mg / L
Statistical analysis
For testing the significance of the differences between two arithmetic means, i.e. the corresponding proportions, the Student t-test is used, when comparing the mean values of the given number of parameters between two groups, such as Wilcoxon- matched test for independent samples. Sensitivity and productivity for positive and negative tests of the examined markers is determined with tests for sensitivity and specificity. The P value of between 0.05 and 0.1 is considered statistically significant. The data processing is made with the statistical package Statistical 7.0.
In the group of 35 patients with RA, DAS 28 > 3.2 was present in 28 patients (80%).
In these 28 patients DAS 2 > 3.2, AAP positive 10 (35.71%) and their M ± SD (1.25 ± 0.43) range (0.85-2.46), g-GT positive were 5 (17.85%) their M ± SD (2.65 ± 0.46) range (0.95-3.45), while β2M was not present in any patient.
In 7 seronegative RF patients with DAS 28 <3>
In standard medical rheumatology, the greatest emphasis is put on Rheumatoid arthritis as the most exposed disease. Seronegative RA is a rare form, difficult to recognize and most often confused with degenerative rheumatism, probably due to their frequency.
Urinary enzyme activity is normally low in the urine and increases when renal tubular cells are excreted [15]. Urinary enzymes, especially NAG, AAP, and AF are very sensitive indicators of parenchymal renal damage in comparison with functional measurements such as glomerular filtration rate (GFR), creatinine and inulin clearance. The relatively low sensitivity of the GFR can be explained by the large renal functional reserve and its large capacity for compensation [16]. There are indications that elevations in urinary enzyme activity may indicate the location of the primary renal tubular damage due to their localization in the brush border area (microsomal AAP) and tubular lysozyme (NAG). They can be used in early diagnosis of acute renal failure because nephrotoxicity is induced by immunosuppressive drugs, contraceptives, antibiotics and cadmium exposure [17-19].
The sensitivity of AAP is higher in comparison with g-GT and β2M. Other standard routine tests used to assess renal function show low sensitivity: creatine in serum and urine, urea in serum. Seronegativity has an impct on the occurrence of AAP enzymuria. This is also present for seronegative patients with DAS 28 > 3.2 who have a much larger AAP induction than DAS 28 < 3>
Non-treated RA primarily affects tubular brush border area and enzymes that derives from this area have increased sensitivity.
AAP has a higher sensitivity than g-GT and β2M in the detection of asymptomatic renal lesions in the non-treated seronegative RA. AAP and g-GT can be used in the everyday clinical practice to diagnose early, asymptomatic renal lesions.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
